Functional Imaging of the Human FEF

描述(申请人提供)：尽管人们普遍认为前额叶皮质(PFC)对于灵活的行动和有效的感知是必要的，但在理解它实现这些目标的控制机制方面存在着根本的差距。这种知识上的差距是一个关键问题，因为许多精神和神经疾病源于执行控制的原发功能障碍。长期目标是了解PFC对运动和感觉系统施加控制的机制。目前提议的目标是测试一种新的模型，即PFC中的活动如何形成标记视野中显著和相关位置的优先空间地图，然后这些地图可以用作执行控制信号的基础。偏向的机制可能涉及用于眼跳规划的机制。该项目的中心目标是测试人类PFC中的神经活动模式与优先图理论的预测相一致的程度，包括优先图的功能组织、优先排序的性质以及优先图读出的效果。提出这项研究的理由是，更好地理解PFC是如何发挥控制作用的，将导致一个强大的理论框架，在此框架内将制定理解精神疾病的策略。本研究的目的将是测试、提炼并可能驳斥优先图理论的原则，这将通过追求三个具体目标来实现：1)确定额叶皮质中显示优先图的特征特征的候选区域--空间地形组织；2)测试候选优先图中的活动是否是各种空间认知使用的基本和一般机制；以及3)确定优先图的读出如何塑造早期视觉皮质的活动。强劲的初步数据证明了项目目标在申请者手中的可行性。在目标1下，利用新颖和优化的地形图绘制方法，在预测预报中心确定了两个候选优先地图。在目标2下，候选优先图中的延迟期活动和大脑活动的多变量模式在各种空间认知任务(如记忆、注意力、计划)中即使不能互换，也是非常相似的。在目标3下，候选优先图中空间特定的持续活动伴随着视网膜定位匹配的早期视觉区域(即V1、V2、V3)的活动，这表明候选优先图中的活动通过其对早期视觉区域中的活动的偏向来指导视觉选择。这种方法具有创新性，因为它具有高度的程序性；它使用新的方法来对抗PFC功能神经解剖学中的个体差异；它以创造性的方式使用强大的新分析方法来严格测试关键假设。这项拟议的研究具有重要意义，因为它有望测试一种重要的执行控制新模型，并将提供对人类PFC实施控制的机制的详细了解，以便将这些机制的功能障碍模型作为神经病理的原因和潜在治疗方法。 公共健康相关性：拟议的研究与公共健康相关，因为我们有必要进一步了解前额叶皮质在正常大脑中实施执行控制的机制，以阐明可能在病理性大脑中出错的机制。具体地说，拟议的研究与NIH的任务相关，因为预计将推进一个更强大的理论框架，在此框架下，临床研究人员可以制定诊断和治疗精神和神经疾病的策略。

DESCRIPTION (provided by applicant): Despite the widespread appreciation that the prefrontal cortex (PFC) is necessary for flexible action and efficient perception, there is a fundamental gap in understanding the control mechanisms by which it accomplishes these goals. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of executive control. The long-term goal is to understand the mechanisms by which the PFC exerts control over motor and sensory systems. The objective of the current proposal is to test a new model of how activity in the PFC forms maps of prioritized space that tag salient and relevant locations in the visual field, which can then be used as the basis of executive control signals. The mechanisms of bias are likely to involve mechanisms used for saccade planning. The central aim of the project is to test the extent to which the patterns of neural activity in the human PFC are consistent with predictions from the priority map theory, including the functional organization of priority maps, the nature of what is prioritized, and the effects of read-out of priority maps. The rationale for the proposed research is that a better understanding of how the PFC exerts control will lead to a strong theoretical framework within which strategies for the understanding of mental disease will develop. The objective will be to test, refine, and possibly refute, tenets of the priority map theory which will be accomplished by pursuing three specific aims: 1) Identify candidate areas in frontal cortex that show the hallmark feature of priority maps - a spatial topographic organization; 2) Test if activity in candidate priority maps is a fundamental and general mechanism used by a variety of spatial cognitions; and 3) Determine how the read out of priority maps sculpts activity in early visual cortex. Strong preliminary data demonstrate the feasibility of project aims in the applicant's hands. Under aim 1, two candidate priority maps were identified in PFC using novel and optimized topographical mapping approaches. Under aim 2, both delay period activity and multivariate patterns of brain activity in candidate priority maps were remarkably similar, if not interchangeable, across a variety of spatial cognition tasks (e.g., memory, attention, planning). Under aim 3, spatially specific persistent activity in candidate priority maps was concomitant with activity in retinotopically matched early visual areas (i.e., V1, V2, V3) suggesting that activity in candidate priority maps guides visual selection via its biasing of activity in early visual areas. The approach is innovative because it is highly programmatic; uses novel approaches to combat individual differences in the functional neuroanatomy of the PFC; and it uses powerful new analytic methods in creative ways to rigorously test key hypotheses. The proposed research is significant because it is expected to test an important new model of executive control and will provide a detailed understanding of the mechanisms by which the human PFC exerts control, such that models of dysfunction of these mechanisms can be targeted as the causes of and potential treatments for neuropathology. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which the prefrontal cortex exerts executive control in the normal brain is necessary to illuminate the mechanisms that could go awry in the pathological brain. Specifically, the proposed research is relevant to NIH's mission because is expected to advance a stronger theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.